Natural History of Heart Failure Allen Circulation 2012 Lanken Am J Respir Crit Care Med 2008

Current Estimate of the Number of Advanced HF Patients Miller and Guglin JACC 2013

Stage D Heart Failure Chronic HF patients whose symptoms persist or decline despite maximal GDMT. They will generally need: Inotropic support Mechanical circulatory device support Transplant Hospice/Palliative care

Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter Maladaptive Mechanisms in Heart Failure Neurohormonal activation Vascular tone Cardiac fibrosis, hypertrophy Sodium retention Endogenous vasoactive peptides (natriuretic peptides, adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) Neprilysin inhibition Neprilysin Inactive metabolites

PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint) 40 Enalapril (n=4212) 1117 32 914 24 LCZ696 (n=4187) Kaplan-Meier Estimate of Cumulative Rates (%) 16 HR = 0.80 (0.73-0.87) P = 0.0000002 Number needed to treat = 21 8 180 360 540 720 900 1080 1260 Days After Randomization Patients at Risk LCZ696 Enalapril 4187 4212 3922 3883 3663 3579 3018 2922 2257 2123 1544 1488 896 853 249 236

HFrEF. Class I Hospital Universitario A Coruña ACEi (or ARB) BB MRA 2012 ESC Guidelines HFrEF. Class I

Guideline directed medical therapy Hospital Universitario A Coruña Yancy, JACC 2013 Guideline directed medical therapy

Non-pharmacologic Optimization of the Heart Failure Patient with Low LVEF Cardiac Resynchronization Therapy (CRT) LVEF <35% NYHA class III – IV QRS > 120 ms Optimal medical therapy

Non-pharmacologic Optimization of the Heart Failure Patient with Low LVEF Implantable Cardiac Defibrillators Ischemic Etiology (Strength of Evidence = A) Non-ischemic Etiology (Strength of Evidence = B) Primary prevention of ventricular arrhythmias LVEF <35% Lindenfeld, J, et al. J Card Failure 2010; 6, 486-491

Acute Heart Failure – What do the New Guidelines Say JJ McMurray EHJ 2012

INTERMACS PROFILES Miller and Guglin JACC 2013

Decision tree for elective mechanical circulatory support in advanced heart failure Peura Circ 2012

Mechanical Circulatory Support Devices Peira Circulation 2012

Advanced Heart Failure Treated with Continuous-Flow Left Ventricular Assist Device NEJM 2009

Comparison of Pulsatile and Continuous Flow Ventricular Assist Devices Slaughter JHLT 2010

Medical Management vs. LVAD Rose, EA; et al NEJM 2001; 345:1435-1443

Survival Rates Kirkland, JK, et. al JHLT 2013; 32:141-156

Survival of Patients with Advanced Heart Failure Treated with Continuous-Flow and Pulsatile Left Ventricular Assist Devices NEJM 2009

Algorithm for Selection of LVAD Candidates Miller and Guglin JACC 2013

Decision tree for elective mechanical circulatory support in advanced heart failure Stewart Circ 2012

VADs– What do the New Guidelines Say JJ McMurray EHJ 2012

VADs– What do the New Guidelines Say

VADs– What do the New Guidelines Say

VADs– Timing is Everything Peura Circulation 2012

VADs– Timing is Everything Peura Circulation 2012

VADs– not for all Peura Circulation 2012

Outcomes of Destination Therapy Clinical Trials NEJM 2009

VADs and Complications • Mechanical wear • Valve dysfunction • Thrombembolic complications

Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis Starling NEJM 2013